A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers

Inclusion Criteria:

• Non-small cell lung cancer with historic PD-L1 ≥ 1%, as determined locally using aclinically accepted assay. Patients must have experienced benefit from previousanti-PD(L)1-containing therapy for at least 4 months based on investigator-assesseddisease stability or response prior to developing documented disease progression.Patients must have also received prior platinum-based chemotherapy, either incombination or in sequence with anti-PD-(L)1, unless patient was ineligible toreceive such treatment.

• Renal cell carcinoma, clear cell histology, previously treated withanti-PD(L)1-containing therapy and a VEGF targeted therapy as monotherapy or incombination. Patients should have documented disease progression followinganti-PD(L)1-containing therapy.

• Cutaneous melanoma, previously treated with anti-PD(L)1-containing therapy. Patientsshould have documented disease progression following anti-PD(L)1-containing therapy.Patients with BRAF V600-mutant melanoma must have also received prior therapy with aBRAF V600 inhibitor, with or without a MEK inhibitor.

• Ovarian cancer, high-grade serous histology, naïve to anti-PD(L)1 therapy, must havereceived one prior systemic therapy in platinum-resistant setting.

• Nasopharyngeal carcinoma, non-keratinizing locally advanced recurrent or metastatic.Depending on the study arm, patients may be naïve to anti-PD(L)1 therapy, orpreviously treated with platinum-based chemotherapy with or without anti-PD-(L)1.

• Locally advanced unresectable or metastatic triple negative breast cancer, ovariancancer (high-grade serous histology), anal cancer (squamous), MSI-H CRC,esophagogastric cancer, mesothelioma, and HNSCC.

• Locally advanced unresectable or metastatic anal cancer (squamous), thymiccarcinoma, MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC, all naïve toanti-PD(L)1 therapy and for whom anti PD(L)1 therapy is not available.

• Triple negative breast cancer with historic PD-L1 CPS ≥ 1%, must have received atleast one line of chemotherapy. In addition, these patients must have previouslyreceived sacituzumab govitecan, and in the case of a BRCA mutation a PARP inhibitor,if these treatments are locally approved and accessible to the patient.

Exclusion Criteria:

• Impaired cardiac function or clinically significant cardiac disease.

• Use of agents known to prolong the QT interval unless they can be permanentlydiscontinued for the duration of study.

• History of severe hypersensitivity reactions to any ingredient of study drug(s) andother mAbs and/or their excipients.

• Active, known or suspected autoimmune disease. Patients with vitiligo, type Idiabetes, residual hypothyroidism only requiring hormone replacement, psoriasis notrequiring systemic treatment or conditions not expected to recur may be considered.Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treatedfor skin rash or with replacement therapy for endocrinopathies should not beexcluded.

• Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior historyof ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.

• Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-relatedtoxicity (applicable to the KFA115 in combination with pembrolizumab treatmentarms).

• Patients with symptomatic peripheral neuropathy limiting instrumental activities ofdaily living.

Other protocol-defined inclusion/exclusion criteria may apply